H2O2 oxidation of [MIII(PyPepS)2]- (M = Fe, Co) complexes with carboxamido nitrogens and thiolato sulfurs as donors affords the corresponding sulfinato [MIII(PyPepSO2)2]- species. The spectral properties of [FeIII(PyPepSO2)2]- resemble those of the iron site of nitrile hydratase.
The Co(III) complexes of N,N'-bis(2-mercaptophenyl)pyridine-2,6-dicarboxamide (PyPSH(4)), a designed pentadentate ligand with built-in carboxamide and thiolate groups, have been synthesized and studied to gain insight into the role of Cys-S oxidation in Co-containing nitrile hydratase (Co-NHase). Reaction of [Co(NH(3))(5)Cl]Cl(2) with PyPS(4)(-) in DMF affords the thiolato-bridged dimeric Co(III) complex (Et(4)N)(2)[Co(2)(PyPS)(2)] (1). Although the bridged structure is quite robust, reaction of (Et(4)N)(CN) with 1 in acetonitrile affords the monomeric species (Et(4)N)(2)[Co(PyPS)(CN)] (2). Oxidation of 2 with H(2)O(2) in acetonitrile gives rise to a mixture which, upon chromatographic purification, yields K(2)[Co(PyPSO(2)(OSO(2))(CN] (3), a species containing asymmetrically oxidized thiolates. The Co(III) metal center in 3 is coordinated to a S-bound sulfinate and an O-bound sulfonate (OSO(2)) group. Upon oxidation with H(2)O(2), 1 affords an asymmetrically oxidized dimer (Et(4)N)(2)[Co(2)(PyPS(SO(2)))(2)] (4) in which only the terminal thiolates are oxidized to form S-bound sulfinate groups while the bridging thiolates remain unchanged. The thiolato-bridge in 4 is also cleaved upon reaction with (Et(4)N)(CN) in acetonitrile, and one obtains (Et(4)N)(2)[Co(PyPS(SO(2)))(CN)] (5), a species that contains both coordinated thiolate and S-bound sulfinate around Co(III). The structures of 1-4 have been determined. The spectroscopic properties and reactivity of all the complexes have been studied to understand the behavior of the Co(III) site in Co-NHase. Unlike typical Co(III) complexes with bound CN(-) ligands, the Co(III) centers in 2 and 5 are labile and rapidly lose CN(-) in aqueous solutions. Since 3 does not show this lability, it appears that at least one thiolato sulfur donor is required in the first coordination sphere for the Co(III) center in such species to exhibit lability. Both 2 and 5 are converted to the aqua complexes [Co(PyPS)(H(2)O)](-) and [Co(PyPS(SO(2))(H(2)O)](-) in aqueous solutions. The pK(a) values of the bound water in these two species, determined by spectrophotometry, are 8.3 +/- 0.03 and 7.2 +/- 0.06, respectively. Oxidation of the thiolato sulfur (to sulfinate) therefore increases the acidity of the bound water. Since 2 and 5 promote hydrolysis of acetonitrile at pH values above their corresponding pK(a) values, it is also evident that a metal-bound hydroxide is a key player in the mechanism of hydrolysis by these model complexes of Co-NHase. The required presence of a Cys-sulfinic residue and one water molecule at the Co(III) site of Co-NHase as well as the optimal pH of the enzyme near 7 suggests that (i) modulation of the pK(a) of the bound water molecule at the active site of the enzyme could be one role of the oxidized Cys-S residue(s) and (ii) a cobalt-bound hydroxide could be responsible for the hydrolysis of nitriles by Co-NHase.
Recent spectroscopic data suggest that the Co(III) site in Co-containing nitrile hydratase is ligated to carboxamido nitrogens and thiolato sulfurs and most possibly one or more of the bound thiolates exist as sulfenato and/or sulfinato groups. The absence of any Co(III) complex with such coordination makes it quite difficult to predict the reactivity of this kind of Co(III) site. In this paper, the Co(III) complexes of two designed ligands PyPepSH2 (1) and PyPepRSH2 (2) have been reported. The two complexes, namely, (Et4N)[Co(PyPepS)2] (3) and Na[Co(PyPepRS)2] (4) are the first examples of Co(III) complexes with carboxamido nitrogens and thiolato sulfurs as donors. The average Co(III)-Namido and Co(III)-S distances in these complexes lie in the range 1.90-1.92 and 2.22-2.24 A, respectively. Reaction of H2O2 with both complexes readily affords Na[Co(PyPepSO2)2] (5) and Na[Co(PyPepRSO2)2] (6), species in which the thiolato sulfurs are converted to sulfinato (SO2) groups. Such conversion also occurs when solutions of 3 and 4 are exposed to dioxygen in the presence of activated charcoal. These reactions are clean and the S --> SO2 transformation does not introduce significant changes in the metric parameters of these complexes. The reactivity of 3 and 4 indicates that the bound Cys-sulfurs around the biological Co(III) site could be oxidized to sulfinato groups.
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